Discover. Oncology最新文献

{"title":"miR-221 is a prognostic marker and promotes the proliferation and migration of esophageal squamous cell carcinoma by inhibiting autophagy.","authors":"Kun Mei, Zilu Chen, Foxing Tan, YuHeng Zhou, Haolin Du, Renjun Gu, Yan Huang","doi":"10.1007/s12672-025-02223-w","DOIUrl":"https://doi.org/10.1007/s12672-025-02223-w","url":null,"abstract":"<p><strong>Purpose: </strong>Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy with high mortality rates. Elucidating the underlying pathophysiological mechanisms of ESCC tumorigenesis is critical for advancing its diagnosis and treatment. MicroRNAs (miRNAs) are pivotal regulators of tumor progression, exerting their effects by binding to target mRNAs and modulating mRNA translation as well as downstream signaling pathways. While the functional roles of numerous miRNAs in ESCC remain incompletely understood, existing studies have implicated autophagy deficiency in aging, cancer, and neurodegenerative diseases. Despite these insights, the relationship between miRNAs and autophagy in ESCC has been insufficiently explored. This study investigates the role of miRNA-221 (miR-221) in ESCC and its interaction with autophagy.</p><p><strong>Methods: </strong>Bioinformatics analysis was employed to determine the biological relevance of miR-221 in ESCC. RT-qPCR was utilized to quantify miR-221 expression in ESCC tissues and cell lines. The effects of miR-221 overexpression or knockdown on cell proliferation and migration were assessed using Cell Counting Kit-8 (CCK8), EdU, and Transwell assays. Western blot analysis was conducted to evaluate autophagy-related changes in ESCC cell lines.</p><p><strong>Results: </strong>The findings demonstrate that elevated miR-221 expression in tissues from patients with ESCC is a potential independent prognostic marker. Overexpression of miR-221 enhances tumorigenic and metastatic capabilities in ESCC cell lines by suppressing autophagy. Notably, rapamycin-induced autophagy activation partially mitigated the tumor-promoting effects of miR-221 on proliferation and migration.</p><p><strong>Conclusion: </strong>The interaction between miR-221 and autophagy presents a promising therapeutic target for ESCC management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"445"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA in colorectal cancer: biology, methods and applications.","authors":"Han Chen, Yang An, Chentong Wang, Jiaolin Zhou","doi":"10.1007/s12672-025-02220-z","DOIUrl":"https://doi.org/10.1007/s12672-025-02220-z","url":null,"abstract":"<p><p>In the practice of colorectal cancer (CRC), traditional tumor tissue analysis is limited by intratumoral and intertumoral heterogeneity and its invasive nature. Circulating tumor DNA (ctDNA) analysis, a promising liquid biopsy approach, has been increasingly explored in clinical studies. Biologically, ctDNA is characterized by tumor-specific diversity and rapid clearance from circulation, enabling real-time, dynamic, and repeatable assessments. Technologically, PCR- and NGS-based downstream analysis methods have been developed and validated. However, variables in pre-analytical and analytical procedures underscores the need for standardized protocols. Compared with clinicopathology-based risk stratification, ctDNA-based molecular residual disease detection has demonstrated significant potential in guiding treatment decisions. Qualitative and quantitative changes in ctDNA have also shown predictive and prognostic value during neoadjuvant or adjuvant treatment, as well as in later-line treatment for metastatic CRC. Specific molecular aberrations in ctDNA can not only assist in identifying candidates for targeted therapies but also reveal resistance mechanisms. Additionally, emerging research is exploring the potential of ctDNA in early cancer detection. Overall, as a novel biomarker, ctDNA holds substantial promise in advancing clinical practice. This review focuses on the biological characteristics, pre-analytical variables, and downstream analysis methods of ctDNA and summarizes its role across various clinical scenarios in CRC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"439"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor NFKB1 mediates TUBB6 to promote the proliferation and suppress apoptosis in glioma via Wnt/β-catenin signaling pathway.","authors":"Yan Li, Ziyu Shao, Jun Jiang, Hongyan Wang, Mei Zhang","doi":"10.1007/s12672-025-02268-x","DOIUrl":"https://doi.org/10.1007/s12672-025-02268-x","url":null,"abstract":"<p><p>Glioma remains one of the most challenging brain tumors with poor prognosis. In this study, we aimed to elucidate the role of TUBB6 in glioma and its potential as a diagnostic and prognostic biomarker. Analysis of the GSE42656 and TCGA datasets revealed that TUBB6 was significantly upregulated in glioma tissues compared to normal tissues. The diagnostic value of TUBB6 was demonstrated with an area under the curve (AUC) of 0.702, suggesting that it could be used as a biomarker to differentiate gliomas Correlation analyses revealed that high TUBB6 expressions were associated with advanced WHO grades, IDH mutation status, and histological types of glioma. Further investigation identified NFKB1 as a key transcription factor that binds to the promoter region of TUBB6, upregulating its expression in glioma cells. Elevated levels of NFKB1 were associated with poor overall survival and disease-specific survival in glioma patients. Knockdown of NFKB1 resulted in reduced TUBB6 expression in glioma cells, confirming the regulatory roles of NFKB1 in TUBB6 expression. Prognostic analysis using TCGA and CGGA datasets demonstrated that high TUBB6 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in glioma patients. TUBB6 was identified as an independent prognostic factor for both OS and DSS. Additionally, pan-cancer analysis revealed that TUBB6 was dysregulated in various tumor types and showed prognostic value across multiple cancers. Functional enrichment analysis of TUBB6-associated differentially expressed genes indicated involvement in immune response, extracellular matrix remodeling, and cytokine signaling pathways. In vitro experiments showed that TUBB6 knockdown suppressed glioma cell proliferation and promoted apoptosis by regulating the canonical Wnt/β-catenin signaling pathway. Our findings suggest that TUBB6 contributes to glioma malignancy through its effects on the Wnt/β-catenin pathway. In conclusion, TUBB6 emerges as a promising biomarker for glioma diagnosis and prognosis. Its regulation by NFKB1 and involvement in key signaling pathways underscore its potential as a therapeutic target for glioma treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"444"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appraising the causal role of cathepsins in genitourinary carcinoma: a two-sample mendelian randomization and prospective study based on 36,225 individuals.","authors":"Qiyu Zhu, Dingbang Liu, Haoyang Liu, Xiaohui Pan, Yifu Shi, Jingjing Guo, Nanwei Tong, Junru Chen, Hao Zeng","doi":"10.1007/s12672-025-02219-6","DOIUrl":"10.1007/s12672-025-02219-6","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin family proteases play an important role in the carcinogenesis of genitourinary carcinomas. However, the causality between serum cathepsin levels and genitourinary carcinomas remains uninvestigated.</p><p><strong>Methods: </strong>In this study, we conducted a two-sample Mendelian Randomization (MR) analysis exploring the causal association between different types of cathepsins and genitourinary carcinomas. Univariate, bidirectional and multivariate MR analyses were conducted based on the genome-wide association studies. Moreover, linkage disequilibrium score regression (LDSC) analysis, colocalization and transcriptomic analysis were also performed. 36,225 Individual data from UK biobank was utilized for further validation.</p><p><strong>Results: </strong>Our findings revealed seven causal associations following univariate analysis, in which five correlations were further validated in multivariate analysis. Cathepsin S (CTSS) was positively associated with papillary renal cell carcinoma (pRCC) [IVW: OR (95%CI) 1.444 (1.103-1.890), p: 8*10-3], and LDSC analysis indicated a genetic correlation between CTSS and pRCC [rg (SE): 0.559 (0.225); p: 0.013]. Other causal correlations included cathepsin B (CTSB), positively associated with testicular non-seminoma, and cathepsin L2 (CTSL2/CTSV), negatively associated with overall kidney cancer and pRCC. Transcriptomic analysis further validated the findings from MR analysis. In the UK biobank, CTSL2 was found to be negatively associated with the risk of cancer of the kidney [HR (95%CI) 0.567 (0.368, 0.873), p: 0.01].</p><p><strong>Conclusions: </strong>Cathepsins played an important role in urogenital carcinogenesis. Further large-scale studies are warranted for extended validation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"435"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization analysis of breast cancer-related ubiquitination modifications over the past two decades.","authors":"Yongxiang Li, Yiyang Wang, Yubo Jing, Youseng Zhu, Xinzhu Huang, JunYi Wang, Elihamu Dilraba, Chenming Guo","doi":"10.1007/s12672-025-02032-1","DOIUrl":"10.1007/s12672-025-02032-1","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitination is a type of post-translational modification, referring to the process in which the small molecular protein ubiquitin covalently binds to target proteins under the catalysis of a series of enzymes. The process of ubiquitination is vital in the onset and progression of breast cancer. The use of the ubiquitin-protease system is expected to be a new way to treat human breast cancer. This research aimed to investigate the evolution patterns, key areas of interest, and future directions of ubiquitination in breast cancer via bibliometric analysis.</p><p><strong>Methods: </strong>Research articles on ubiquitination modifications in breast cancer were sourced from the Web of Science Core Collection database and analyzed via Microsoft Excel 2021, Bibliometrix, VOSviewer, and Citespace software for thorough bibliometrics.</p><p><strong>Results: </strong>From 2005-2024, 1850 English articles published in 405 journals by 1842 institutions/universities from 61 countries were included in the study. Keywords, research fields, co-cited literature and other information were included. Research on ubiquitination modifications has focused on breast cancer, expression, protein, activation, degradation, ubiquitination, phosphorylation, etc. Notably, the keywords that broke out in the past five years have focused on \"triple-negative breast cancer\", \"promotion\", and \"metabolism\". These findings suggest that key areas of current research are metabolism, immunity, survival, and prognosis in triple-negative breast cancer.</p><p><strong>Conclusions: </strong>Our findings indicate that research on triple-negative breast cancer, as well as its immunological and metabolic aspects, is a burgeoning and promising area. Our work offers valuable guidance and fresh perspectives on the relationship between breast cancer and ubiquitin modification.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"431"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of new autoantibodies in urothelial bladder cancer for biomarker discovery using immunoproteomics.","authors":"Samira Tabaei, Mohammadrasul Zareinejad, Mohammad Reza Haghshenas, Nasser Shakhssalim, Kambiz Gilany, Allan Stensballe, Abbas Ghaderi","doi":"10.1007/s12672-025-02167-1","DOIUrl":"10.1007/s12672-025-02167-1","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated antigens (TAAs) lead to the production of tumor-specific autoantibodies (anti-TAA autoantibodies) by triggering the humoral immune system which can be used as candidate biomarkers. This study aims to investigate TAAs proteins eliciting humoral responses in different stages of urothelial bladder carcinoma (UBC) using an immunoproteomics approach to find novel biomarkers for the clinical management of the disease.</p><p><strong>Methods: </strong>Total proteins were obtained from the newly established UBC cell line, JAM-ICR, and separated by two-dimensional gel electrophoresis (2DE). These proteins were then immobilized using pooled serum samples from healthy individuals, autoimmune and UBC patients at different stages. The immunoreactive spots in UBC patient samples were identified by mass spectrometry and verified with several databases such as GEPIA and Enrichr databases.</p><p><strong>Results: </strong>Through the comparison of the immunoreactivity pattern of serums, we were able to identify eight specific proteins using LC-MS. Patients with muscle invasion showed increased expression of ENO1, VDAC2, AKR1B1, SDF2L1, PRDX6, PSME1, HSPB1 and PHB1 compared to controls. In addition, non-muscle invasive patients showed overexpression of ENO1, VDAC2, AKR1B1, and PRDX6 compared to controls. In addition to their diagnostic function, PRDX6, ENO1, VDAC2, and PHB1 have been demonstrated to possess prognostic capabilities in patients with UBC. Interestingly, these proteins were mainly associated with cellular growth and anti-apoptotic activity.</p><p><strong>Conclusion: </strong>In this study, eight anti-TAA autoantibodies were identified that have the potential to serve as diagnostic and prognostic biomarkers. These could represent a valuable panel of biomarkers for the management of UBC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"436"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the signaling pathway mechanism of terpenoids against breast cancer.","authors":"Sheng-Nan Tu, Fen Hu, Juan Zhang, Haifeng Cai, Junquan Yang","doi":"10.1007/s12672-025-01881-0","DOIUrl":"10.1007/s12672-025-01881-0","url":null,"abstract":"<p><p>Breast cancer is the most common malignant tumor in women worldwide. Current treatments include chemotherapy, hormone therapy, radiotherapy and surgery. Terpenoids have great anti-cancer potential due to their anti-inflammatory, antioxidant, anti-tumor, antiviral and other biological activities. They have become the central drug for the prevention and treatment of breast cancer. However, their low bioavailability and stability are urgent issues that need to be addressed. This article aims to sort out the mechanism of action of terpenoids in the treatment of breast cancer. By reviewing different signal transduction pathways, it is hoped that new ideas for the joint action of multiple pathways and multiple targets will be provided, and a theoretical basis will be provided for improving basic research and clinical treatment of breast cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"433"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the association between 91 circulating inflammatory proteins and the risk of carcinoid syndrome: a Mendelian randomization analysis.","authors":"Jingzhi Wang, Simin Peng","doi":"10.1007/s12672-025-02147-5","DOIUrl":"10.1007/s12672-025-02147-5","url":null,"abstract":"<p><p>This study aims to explore the potential correlation between circulating inflammatory proteins and carcinoid syndrome (CS). Using summary data from genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) analysis with two samples, treating 91 circulating inflammatory proteins as exposure factors and CS as the outcome. Based on genetic loci closely associated with circulating inflammatory proteins selected as instrumental variables, we primarily employed the inverse-variance weighted (IVW) method for analysis, combined with the weighted median method (WM), simple median method (SM), weighted mode estimation (WME), and MR-Egger regression for comprehensive analysis. Initial IVW results revealed significant causal effects of six circulating inflammatory proteins on CS. Specifically, Interleukin-17C levels were negatively correlated with CS risk, indicating a protective effect; whereas beta-nerve growth factor, C-C motif chemokine 20, Natural killer cell receptor 2B4, C-X-C motif chemokine 5, and Leukemia inhibitory factor levels were positively correlated with CS risk, suggesting detrimental effects. In heterogeneity tests, the selected single-nucleotide polymorphisms (SNPs) did not show heterogeneity, and analysis using Egger intercept and MR-PRESSO test did not detect pleiotropy of SNPs, thus validating the reliability of the study. Furthermore, sensitivity analysis using the leave-one-out method further confirmed the robustness of the results. In summary, this study identified significant causal relationships between six inflammatory proteins-Interleukin-17C, beta-nerve growth factor, C-C motif chemokine 20, Natural killer cell receptor 2B4, C-X-C motif chemokine 5, and Leukemia inhibitory factor-and CS risk through MR analysis. This finding not only emphasizes the important role of inflammation in the pathogenesis of CS but also suggests the potential value of inflammatory proteins as targets for early diagnosis and therapeutic interventions.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"434"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the effect of modifiable risk factors on hepatocellular carcinoma: evidence from a bidirectional Mendelian randomization analysis.","authors":"Lijuan Wei, Enci Ding, Dongyan Lu, Zhongying Rui, Jie Shen, Guoju Fan","doi":"10.1007/s12672-025-02177-z","DOIUrl":"10.1007/s12672-025-02177-z","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of hepatocellular carcinoma (HCC) involves a variety of environmental risk factors, some of which have yet to be fully clarified. Using the Mendelian randomization (MR) approach, this study comprehensively investigates the causal effect of genetically predicted modifiable risk factors on HCC.</p><p><strong>Methods: </strong>Genetic variants related to the 50 risk factors that had been identified in previous research were derived from genome-wide association studies. Summary statistics for the discovery cohort and validation cohort of HCC were sourced from the FinnGen consortium and the UK Biobank, respectively. Bidirectional MR analysis and sensitivity analysis were performed to establish causative risk factors for HCC.</p><p><strong>Results: </strong>Through the inverse variance weighted method, the results of the discovery cohort indicated that waist circumference, nonalcoholic fatty liver disease (NAFLD), alanine aminotransferase (ALT) levels, and aspartate aminotransferase (AST) levels were significantly linked to HCC occurrence risk. Furthermore, body fat percentage, glycated hemoglobin (HbA1c), obesity class 1-3, waist-to-hip ratio, iron, ferritin, transferrin saturation, and urate had suggestive associations with HCC. The validation cohort further confirmed that NAFLD and ALT levels were strongly related to HCC. Reverse MR indicated that genetic susceptibility to HCC was connected to NAFLD and transferrin saturation. Sensitivity analyses showed that most of the findings were robust.</p><p><strong>Conclusion: </strong>This MR study delivers evidence of the complex causal relationship between modifiable risk factors and HCC. These findings offer new insights into potential prevention and treatment strategies for HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"437"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer activity of Stemona tuberosa (wild asparagus) against type-II human lung adenocarcinoma (A549) cells and identification of SRC inhibitor using integrated network pharmacology and molecular dynamic simulation.","authors":"C Lalmuansangi, Lalfakawmi, Fanai Nghakliana, Hmingremhlua Sailo, Lalchhandami Tochhawng, Amit Kumar Trivedi, Kiran R Kharat, Balachandar Vellingiri, Nachimuthu Senthil Kumar, Zothan Siama","doi":"10.1007/s12672-025-02138-6","DOIUrl":"https://doi.org/10.1007/s12672-025-02138-6","url":null,"abstract":"<p><p>Stemona tuberosa is widely recognized for its traditional applications as an anti-cancer agent. This study aimed to assess the anti-cancer properties of S. tuberosa in human lung adenocarcinoma A549 cells. Among the various solvent extracts of S. tuberosa, the methanolic extract showed the highest toxicity against A549 cells. The S. tuberosa extract elicited cytotoxic effects and suppressed colony formation in A549 cells in a dose-dependent manner. S. tuberosa activity was further supported by AO/EtBr staining, increased caspase 3/6 activity, upregulation of pro-apoptotic genes, DNA damage, and elevated lipid peroxidation, with decreasing antioxidant levels. LC-MS analysis identified 80 predominant secondary metabolites in the methanolic extracts of S. tuberosa. A network pharmacology study identified SRC as the primary target of compounds identified from S. tuberosa. SRC protein is crucial for advancing lung cancer because of its function in cell proliferation, survival, and metastasis. Among the various compounds identified from S. tuberosa extract, 4-Azatricyclo [4.3.1.13,8] undecan-5-one (ADE) (- 10.88 kcal/mol) and Dihydro-normorphine, 3-desoxy- (DNY) (- 10.83 kcal/mol) exhibited notable binding affinities for SRC. Further analysis using molecular dynamics simulations (100 ns) validated the stability of SRC-ligand complexes, with RMSD of 1.8 and 2.2 Å for ADE and DNY, respectively, alongside the establishment of essential hydrogen bonds with pivotal residues, including ASP408, ALA403, and THR438. Finally, gmx._MMPBSA showed favourable ΔGbind values for ADE (- 15.06 ± 0.11 kcal/mol) and DNY (- 15.66 ± 0.25 kcal/mol), which highlights the significant potential of ADE and DNY as effective SRC inhibitors, suggesting S. tuberosa as a novel candidate for cancer therapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"429"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}